During the sixteenth year, Program-Project HL08682 investigators studied cardiovascular regulation including central, spinal, and peripheral autonomic nervous control, biochemical and metabolic regulation, endotoxin shock, cardiopulmonary integration, transmembrane ion transport, catecholamine metabolism, pulmonary circulaion, and the regulation of hibernation and arousal. The research resulted in animal models of surgically selective denervation of the heart, development of a canine model of Sick Sinus Syndrome, and studies of coronary collateral flow channels and myocardial performance with and without cardiac denervation. Peritoneal macrophages elaborate a mediator which stimulates adipose glucose oxidation. Its insulin-like activity suggested the descriptive term macrophage insulin-like activity (MILA) for the mediator. Endotoxemia elicits hypersecretion of insulin. RES depression (by colloidal carbon or lead acetate) also results in hypersecretion of insulin from the isolated pancreas in response to a glucose stimulus. Thus, altered states of insulin regulation may be related to increased sensitivity to endotoxin shock caused by RES depression, suggesting a possible control mechanism for RES modulation of insulin secretion. An isolated heart model was developed for study of myocardial regulation in hibernation and hypothermia. Myocardial responses of hybernating species were examined during hypoxemia and ischemia. Oxygen consumption and autoregulation of coronary blood flow were studied. Enzymatic digestion with elastase and collegenase revealed that the dog carotid artery's elastic characteristics are attributable to elastin. Ascending spinal pathways for somatovagal and somatosympathetic fibers were described. Ultrastructure of sympathetic preganglionic neurons and synaptic boutons were examined. Atrial subsidiary pacemakers following excision of the sinoatrial node were localized. Pulmonary dynamic parameters during nitroprusside, carotid occlusion, and during acute lung injury were reported. Inspiratory off-switch characteristics were assessed utilizing models of intercostal afferent stimulation. This intercostal reflex operates directly on brainstem neurons, independent of any cerebellar connections. Hypercapnia, hypoxia, hyperoxia change off-switch.